Nasal Nitric Oxide in Chronic Rhinosinusitis with or without Nasal Polyps: A Systematic Review with Meta-Analysis

Background and Aims: There has been a recent growing interest in the role of nasal nitric oxide (nNO) as a biomarker for osteomeatal complex obstruction in paranasal sinus diseases. By using meta-analysis, we systematically reviewed the literature to establish the possible link between nNO concentration and chronic rhinosinusitis with nasal polyps (CRSwNP) or without (CRSsNP). Methods: We systematically searched the EMBASE, PubMed, Scopus, and Web of Science databases for related studies. Differences between controls and cases were reported as standardized mean difference (SMD), with 95% confidence intervals (95% CI), using the random-effects method. Results: We selected 23 articles for the final analysis: 15 with data on 461 CRSwNP patients and 384 healthy controls, 10 with data on 183 CRSsNP patients and 260 controls, and 14 studies on 372 CRSwNP and 297 CRSsNP patients. CRSwNP patients showed significantly lower nNO values when compared to both healthy controls (SMD: -1.495; 95% CI: -2.135, -0.854; p < 0.0001) and CRSsNP patients (SMD: -1.448; 95% CI: -2.046, -0.850; p < 0.0001). Sensitivity and subgroup analyses confirmed the results, which were further refined by regression models. They showed that an increasing aspiration flow is related to a greater difference in nNO levels between cases and control subjects. We also documented lower nNO levels in CRSsNP patients with respect to controls (SMD: -0.696; 95% CI: -1.189, -0.202; p = 0.006), being this result no longer significant when excluding patients in therapy with intranasal corticosteroids. As shown by regression models, the increased Lund-Mackay score indicates a high effect size. Conclusions: nNO levels are significantly lower in CRSwNP, especially when using higher aspiration flows. Additional studies are needed to define one single standardized method and normal reference values for nNO.